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At least 1,531 records · Page 85Linked to original sources
PubMed1982

Protection against colibacillosis in neonatal piglets by immunization of dams with procholeragenoid.

Protection against colibacillosis in neonatal piglets was obtained by immunization of pregnant dams with procholeragenoid. Procholeragenoid is a stable high-molecular-weight aggregate of cholera toxin formed during the heating of cholera toxin. Procholeragenoid retained approximately 1% of the toxicity of native toxin as determined in the rabbit ileal loop and Y-1 adrenal cell assays and 5% of the activity in the rabbit skin assay. Immunization of pregnant dams with 50 micrograms of procholeragenoid 5 and 2 weeks before the expected delivery date elicited high titers of antitoxic immunoglobulin G and toxin-neutralizing antibody in both the colostrum and serum. In three independent field trials, immunization with procholeragenoid resulted in a substantial decrease in diarrhea (73% in controls versus 11% in immunized) and death (4.7% in controls versus 0.77% in immunized) in neonatal piglets. The protection rate in the immunized population was approximately 85% for both diarrhea and death. In the following gestation period, reimmunization of dams with a single dose of procholeragenoid (50 micrograms) 2 weeks before delivery elicited titers of antitoxic immunoglobulin G and toxin-neutralizing antibody comparable to those obtained during the primary immunization. The death rate in neonatal piglets (0.86%) was comparable to that seen after immunization during the first gestation period (0.77%). These results indicate that substantial protection of neonatal piglets against colibacillosis can be obtained by immunization of dams with procholeragenoid. Protection was found to be based solely on antitoxic immunity.

Animals↗
PubMed1996

Requirements for valid alternative assays for testing of biological therapeutic agents.

Several novel toxin-derived biological therapeutic products are now available or under development. There is thus an increasing need to develop alternative assays for their efficacy testing, which currently still depends largely on in vivo methods. Scientific advances in the understanding of the mode of action of these substances has not only fuelled the pace of their development as therapeutic agents but has also provided the basis for improving upon conventional testing procedures.

Animal Testing Alternatives↗
PubMed1984

Immune response and reactions to various dose regimens for raising hyperimmune antisera in sheep.

To determine the optimum procedure for raising hyperimmune sera to tetanus toxin, three adjuvants, four antigen preparations and two routes of administration in various combinations were investigated in sheep. Oil-in-water adjuvants alone or in combination with aluminum gels were superior to aluminium gels on their own. This disadvantage of aluminium gels was partially but not completely abrogated when the frequency of doses was increased to three per week. Intensity of local reaction was strongly correlated with immune response; the more immunogenic a dose, the more reactive. Reactivity of oily adjuvants could be lessened by use of a more suitable route of administration, thus oily adjuvants appeared suitable for use when administered by the intraperitoneal route even though moderate to severe reactions resulted from subcutaneous injections. Of other variables investigated, toxin did not confer any advantage over toxoid as an immunogen, purified toxoid was a significantly better immunogen than unpurified toxoid and two large bleeds (30% of total blood volume each) every six weeks rather than 20 ml test bleeds did not affect the titre of the hyperimmune serum produced.

Adjuvants, Immunologic↗
PubMed2002

[Botulism: the agent, mode of action of the botulinum neurotoxins, forms of acquisition, treatment and prevention].

The botulinum neurotoxins are produced by anaerobic, spore-forming bacteria belonging to the Clostridium genus. They are synthesised as a single chain protein (150 kDa), which is not or weakly active. The active form results from a proteolysis cleaving the precursor in a light chain (about 50 kDa) and a heavy chain (about 100 kDa), which are linked by a disulfide bridge. The heavy chain is involved in the recognition of a specific neuronal surface receptor and mediates the internalization of the light chain into the cytosol. The light chain is responsible for the intracellular activity. It catalyses the proteolysis of SNARE proteins, which are involved in the exocytosis of synaptic vesicles containing acetylcholine. Hence, the release of acetylcholine at the neuromuscular junction is blocked, leading to a flaccid paralysis. Human botulism, usually type A, B or E, is associated with intoxination, ingestion of preformed toxin in food, with digestive toxi-infection, mainly in newborns (infant botulism), or with wound contamination (wound botulism). The treatment of botulism is usually symptomatic. The specific treatment is based on the serotherapy or on the use of purified specific antibodies. The vaccination against botulism is efficient. However, since the botulinum neurotoxins are widely used for the treatment of numerous dystonias, a generalised vaccination is not conceivable.

Bacterial Vaccines↗
PubMed1987

Effects of cycloheximide and puromycin on cytotoxic activity of Escherichia coli verocytotoxin (Shiga-like toxin).

Verocytotoxin (VT)-producing Escherichia coli is closely associated with hemorrhagic colitis and hemolytic uremic syndrome. The diagnosis of this infection requires the demonstration of VT activity in fecal filtrates or the isolation of VT-producing E. coli from stools. To improve the sensitivity of the Vero cell assay for detecting VT, we investigated the interaction between this toxin and cycloheximide and puromycin, agents which, like VT and the related Shiga toxin, are protein synthesis inhibitors. Cycloheximide-treated cells were found to be about eightfold more sensitive to VT, this effect being most pronounced when the drug was added before the toxin. In contrast, puromycin treatment had an antagonistic effect in that it decreased the sensitivity of the cells to VT. In assays of VT in fecal filtrates, the addition of cycloheximide (at 4 to 8 micrograms/ml) increased the sensitivity without affecting the specificity of the assays. Likewise, the use of cycloheximide led to an increase in the sensitivity of the serum VT-neutralizing antibody test by a factor of over eightfold.

Animals↗
PubMedDate not supplied

Protection against tetanus toxin in mice nasally immunized with recombinant Lactococcus lactis expressing tetanus toxin fragment C.

Mice inoculated intranasally (i.n.) with a recombinant strain of live Lactococcus lactis expressing tetanus toxin fragment C (TTFC), produced both serum and secretory antibodies to TTFC. Killed bacteria which had accumulated TTFC intracellularly in vitro also elicited protective serum antibody responses. There was no requirement for either colonization or invasion of the mucosa. In addition secretory antibody responses in the lung and nasal tissues were elicited after i.n. inoculation in the presence of an adjuvant.

Administration, Intranasal↗
PubMed1994

Retrospective study of 108 cases of botulism in Poitiers, France.

Botulism, a food-borne toxin-mediated disease caused by Clostridium botulinum is still a common disease, which is most frequent in the rural environment; 108 cases, 66 males and 42 females, average age 32 years, were recorded from 1965 to 1990 in the infectious disease department of the University Hospital of Poitiers (France). In 83% of patients, the food responsible was home-cured ham. Mean incubation time was 3.4 days; digestive symptoms were observed in 93% of cases, ocular symptoms in 92% and urinary tract dysfunction in 22%. A scale of severity was used to classify the patients into those suffering from severe (6), intermediate (50) and mild (52) forms of the disease. Botulinum toxin type B was found in 36 (52%) of 69 blood samples and in 41 (51%) of 81 samples of the suspected food. From 1965 to 1976, 44 patients were treated with both toxoid and heterologous equine serotherapy. Since 1976, 29 patients have been treated with guanidine hydrochloride (35 mg/kg daily) and 35 patients with guanidine hydrochloride plus heterologous serotherapy. All 108 patients recovered without any sequelae.

Adolescent↗
PubMed1980

[Production of a homogeneous Cl. botulinum type B neurotoxin].

The method for obtaining the neurotoxin, or alpha-fraction of the toxin, of Cl. botulinum, type B, is described. In accordance with this method, the toxin was precipitated three times with hydrochloric acid in the isoelectric zone with subsequent extraction with phosphate (pH 6.8) and citrate-phosphate (pH 5.6) buffers, then fractionated in columns with DEAE cellulose (pH 5.6), DEAE Sephadex A-50 (pH 7.2) and Sephadex G-200 (pH 7.2). The homogeneous neurotoxin preparations with molecular weights ranging from 145,000 to 160,000 and having the isoelectric point at pH 5.5 and toxicity 5.0--10.0 x 10(7) Dlm per 1 mg protein were obtained.

Animals↗
PubMed1988

[Enhancement of antitoxic immunity in newborn infants by peroral administration of donor antistaphylococcal immunoglobulin].

The possibility of enhancing specific immunity by the oral administration of homologous antistaphylococcal immunoglobulin in a dose of 50 I. U./kg b. w. before the first feeding was shown in 75 newborn infants with a high risk of staphylococcal infection. 24 hours after the first administration of Ig the titer of staphylococcal anti-alpha toxin in the blood rose from 0.68 +/- 0.05 I. U./ml to 2.9 +/- 0.14 I. U/ml, on day 7 this titer persisted at the level of 2.86 +/- 0.12 I. U./ml, and 3 months later the titer was 1.5 +/- 0.05 I. U./ml. No side effects were observed. In the reference group (50 infants) antitoxic titers remained low. No suppurative-septic diseases were observed in the test group within 3 months, while in the controls, focal forms of staphylococcal infection (12 cases) and sepsis (1 case) were registered.

Administration, Oral↗
PubMedDate not supplied

Botulism in China.

During the period 1958-1983, 986 outbreaks of botulism occurred in China, affecting 4,377 individuals and resulting in 548 deaths. The initial cases of botulism were found in Xinjiang province, where the incidence was highest. Outbreaks have occurred in all of the northern provinces and in some of the southern provinces of China. The toxin found most frequently in the northwest region of China was type A; in north China, type B; and in the northeast, type E. The most frequently offending food was home-made strong-smelling preserved bean curd, which was implicated in 74% of the outbreaks. The complex clinical manifestations of botulism can be grouped into those affecting the eyes, the mouth, the pharynx, and the skeletal muscles. Following the institution of effective methods of prevention and treatment, epidemics of botulism in China have been controlled and the mortality rate reduced from 41% (1950s) to 7.6% (1983).

Animals↗
PubMed2000

Influence of codon usage on the immunogenicity of a DNA vaccine against tetanus.

Two related DNA vaccine vector plasmids, harbouring either wild-type (pcDNA3/ntetC) or synthetic codon optimised (pcDNA3/stetC) DNA encoding fragment C (TetC) of tetanus toxin were constructed. COS-7 cells transformed with pcDNA3/stetC reproducibly expressed higher levels of TetC than similar cells transformed with pcDNA3/ntetC. BALB/c mice immunised intramuscularly with pcDNA3/stetC produced significantly higher levels of anti-TetC antibodies in their serum in the weeks following vaccination compared to mice immunised with pcDNA3/ntetC, even when differences in the CpG content between the two sequences were controlled for using non-expressing DNA.

Animals↗